Pre-clinical Vaccine Development for Respiratory Viruses

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Human paramyxoviruses and pneumoviruses are widespread pathogens, cause considerable disease burden. Parainfluenza virus types 14 (PIV14) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised individuals. Based on a cryoelectron microscopy structure of an engineered PIV3 F prefusion-stabilized trimer, we engineered mutations in each of the four PIV fusion (F) glycoproteins to stabilize their metastable prefusion states. The vaccine candidates were able to elicit murine PIV type-specific response, with little cross-neutralization of other PIVs. In nonhuman primates (NHPs), quadrivalent immunization with prefusion-stabilized Fs from PIV14 consistently induced potent neutralizing responses against all four PIVs.